Deciphering tRNA repertoires and translation coordination during mouse early embryogenesis by ORACLE-tRNAseq

Area of Science:

• Developmental Biology
• Molecular Biology
• Genomics

Background:

• Translational control is crucial for the maternal-to-zygotic transition (MZT) in early embryogenesis.
• Characterizing embryonic transfer RNA (tRNA) pools has been challenging due to low cell input.

Purpose of the Study:

• To develop a sensitive method for profiling tRNA from limited embryonic samples.
• To map the dynamic changes in tRNA repertoires during early mouse development.
• To investigate the coordination between tRNA availability and zygotic genome activation (ZGA).

Main Methods:

• Optimized Reaction for Accurate Capture of Low-input Entities tRNA Sequencing (ORACLE-tRNAseq) was developed for robust tRNA profiling from as few as five mouse oocytes.
• tRNA landscapes were mapped from oocyte to blastocyst stages.
• Integrated multi-omics analyses, including Ribo-seq, were performed.

Main Results:

• ORACLE-tRNAseq enabled detailed mapping of tRNA landscapes during early embryogenesis.
• A distinct transition to embryonic tRNA repertoires was identified, with upregulation of tRNA pseudogenes at the 4-cell stage.
• Zygotic tRNA gene activation, coinciding with ZGA, was linked to chromatin remodeling (H3K4me3).
• Embryonic tRNA anticodon pools were shown to coordinate with highly translated genes, establishing zygotic translation machinery post-ZGA.

Conclusions:

• The study presents ORACLE-tRNAseq as a powerful tool for low-input tRNA profiling in developmental contexts.
• Findings elucidate the dynamic regulation of tRNA pools and their critical role in coordinating translation with zygotic genome activation.
• This work provides a foundational resource for understanding translational control during early embryogenesis.